Our major emphasis continues to be to study the role of restriction modification systems of Haemophilus in transformation. Considerable effort has been focused on preparing mutations in the restriction modification systems and examining their effects on transformation. In the case of H. influenzae type d it is difficult to obtain pure mutant populations because of the problem of segregation. Examination of mutants in restriction and modification of H. influenzae type b and H. aegyptius demonstrate a loss of transforming activity that parallels a loss in restriction and modification. In some cases it appears that the role of modification may be more critical than that of restriction. Methylase activities that protect unmodified DNA from inactivation by its corresponding restriction activity have been isolated and shown to have a very high level of specificity. However, at least one methylase was obtained that acts on its own DNA i.e. a methylase from H. influenzae type d can methylate DNA from the same strain. The degree of methylation is too high to assign it to the activity for the Type 1 enzyme Hind 1. We therefore propose either that H. influenzae greatly under methylates its DNA or that the methylase has been altered to reduce its specificity. Alterations in specificity during preparation is also argued for other endonucleases such as Hind 1,11,111.